Dabigatran - A medication update

ANF iFOLIO CLINICAL UPDATE: Dabigatran - A medication update Dabigatran - A medication update Read this article and complete the quiz to earn 0.5 iFolio hourRead this article and complete the quiz to earn 0.5 iFolio hour

Generic name: Dabigatran Brand name: Pradaxa Drug class: Direct thrombin inhibitors

INDICATIONS FOR USE

Dabigatran is used to prevent venous thromboembolism (VTE) in individuals with nonvalvular atrial fibrillation (AF) and a high risk of stroke and following elective total hip or knee replacement. It is also used to treat acute VTE and prevent further thrombus formation.1 severe bleeding.1 Seek specialist advice prior to the insertion or removal of spinal or epidural catheters.1

In those who require surgery, stop dabigatran several days in advance depending on renal function (see Table 1).1 Intravenous heparin or subcutaneous low molecular weight heparin may be used up until surgery for those at high risk of blood clots.1

Table 1. Recommendations for the cessation of dabigatran prior to surgery1

MECHANISM OF ACTION

Direct thrombin inhibitors bind to thrombin and prevent the conversion of fibrinogen to fibrin as well as the aggregation of platelets in the bloodstream (see Illustration 1).1

Illustration 1: A simplified coagulation cascade

PRECAUTIONS

Contraindications for dabigatran include gastrointestinal bleeding in the past 12 months, prosthetic heart valves, severe renal failure (creatinine clearance, CrCL<30mL/minute), and liver disease (liver enzymes more than two times the upper limit of normal).1 Alternate dosages may be required for the elderly (over 75 years of age) and those with renal impairment (CrCl 30-50mL/minute).1 Direct thrombin inhibitors should also not be used in individuals with severe acute bleeding or an increased risk of

Renal Function (CrCl)

>50mL/minute

30-50mL/minute

Recommendations for stopping dabigatran prior to surgery

One to three days prior to elective surgery Three to five days prior to surgery

In emergencies, a reversal agent (idarucizumab) may be used to reverse the effects of dabigatran.2 Idarucizumab is a specific nonvitamin K antagonist oral anticoagulant reversal agent that has been shown to safe and effective in clinical trials. Safety data continues to develop as use in hospitals increases.2 Dabigatran is associated with several drugdrug interactions. Use is discouraged or contraindicated in those taking a variety of other medications including;1

• Oral ketoconazole (concurrent use is contraindicated) • P-gp inhibitors or inducers, such as amiodarone or carbamazepine (use cautiously or avoid use) • Verapamil (concurrent use is contraindicated) Evidence for use in pregnancy and breastfeeding is limited. Alternative medications are recommended.1 Compared to warfarin,

Table 2. Indication, dosage and duration of treatment for dabigatran1

Indication Dosage Duration of treatment

Prevention of VTE post-hip and knee replacement

Atrial fibrillation

Acute VTE and prevention of subsequent VTE 110mg within 1-4 hours of surgery, followed by 220mg once daily With amiodarone or verapamil or CrCl 3050mL/minute: 150mg once daily 150mg twice daily >75 years, CrCl 30-50mL/minute, severe risk of bleeding: 110mg twice daily Commence dabigatran after five days of parenteral anticoagulation 150mg twice daily >75 years, CrCl 30-50mL/minute, severe risk of bleeding: 110mg twice daily At least three months

10 days (post-knee replacement) 28-35 days (post-hip replacement)

N/A dabigatran has also been shown to increase the risk of myocardial infarction in clinical trials.1

ADVERSE EFFECTS

Dabigatran has the potential to cause gastritis, dyspepsia, and gastrointestinal bleeding. It may also cause oesophageal ulcers, increased liver enzymes and bilirubin, and an increased risk of bleeding. Severe bleeding is rare with dabigatran.1

DOSAGE AND ADMINISTRATION

Dabigatran is administered orally. The dose and duration of treatment is dependent on the indication (see Table 2).1

SWITCHING ANTICOAGULANTS

It is common to switch between anticoagulants as a patient’s condition changes. For example, someone may start on parenteral anticoagulation prior to commencing long-term dabigatran or may switch between warfarin and dabigatran based on side effects.1 If changing from dabigatran to parenteral anticoagulation wait 12 to 24 hours before the last dabigatran dose (depending on the indication).1 If using dabigatran after parenteral anticoagulation, start dabigatran two hours before the next dose of parenteral anticoagulation would have been due.1

Changes between dabigatran and warfarin are based on INR and CrCl. When changing from warfarin to dabigatran, wait until INR is less than two.1 When changing from dabigatran to warfarin, start warfarin 1 to 3 days prior to stopping dabigatran depending on CrCl.1

ADVICE AND EDUCATION

Dabigatran should be swallowed whole, at the same time every day, with water and food.1 Monitor renal function and for signs of bleeding, such as unexplained bruising, discoloured urine or faeces.1 In a medical emergency, it is essential that healthcare professionals know an individual is taking dabigatran. A medical alert bracelet may be recommended.1

REFERENCES

1. Australian Medicines Handbook 2018 (computer program). Adelaide: Australian Medicines

Handbook Pty Ltd; 2018 January. 2. NPS MedicineWise. Idarucizumab (Praxbind) for dabigatran (Pradaxa) reversal: what you should know [Internet]. Surry Hills: NPS

MedicineWise; 2017 Apr 19 [cited 2018

Apr]. Available from: https://www.nps. org.au/medical-info/clinical-topics/news/ idarucizumab-praxbind-for-dabigatranpradaxa-reversal-what-you-should-know